ESTRO 36 Abstract Book

S531 ESTRO 36 _______________________________________________________________________________________________

In the present study we examined the relative sensitivity of various tumor cells in vivo and in vitro to alpha radiation and the role of DNA damage control in this effect. Material and Methods Implanted murine tumors were treated with a single 224 Ra- loaded source, and tumor progression and survival were recorded. Intratumoral alpha particle distribution was measured by the spread of 212 Pb. The sensitivity of the various cancer cells was determined by their ability to form colonies after irradiation in vitro with alpha particles. The formation and disappearance of g amma- H2AX foci (DSBs indicators), and activation of non- homologous end joining following recruitment of Ku70 into the nucleus, served to evaluate DNA damage control and - DaRT caused significant damage in vivo to squamous cell tumors (SQ2) but not to pancreatic (Panc02) and breast adenocarcinoma (4T1). - Tissue necrosis and tumor growth retardation were in correlation with the intratumoral distribution of released alpha emitting isotopes. - SQ2 cells were the most radiosensitive to alpha particles (mean lethal dose required to reduce cell viability to 37%; D 0 =0.57) while the pancreatic (D 0 =1.1) and breast cancer cells (D 0 =1.05) were less radiosensitive. - The three cell lines exhibited different damage accumulation and repair kinetics. The radio-resistant cell line 4T1 had the lowest number of double strand breaks (DSBs) and a fast recruitment of nuclear Ku70, indicating a quick and efficient repair process. The relatively radio- resistant Panc02 cells, had an intermediate number of DSBs, and fast damage repair. SQ2 cells exhibited high DNA damage and a low and very slow Ku70 nuclear recruitment, indicating a slow and not efficient repair process that consequently resulted in cell death. Conclusion The radiosensitivity of tumors to alpha radiation was in correlation with their ability to avoid or repair double strand breaks. Identifying the mechanism(s) responsible for the resistance of various tumor cells to alpha radiation may open the possibility to block this mechanism(s) and render the cells more susceptible to alpha particles. This may have practical implications for the treatment of solid tumors by DaRT. PO-0962 Proton minibeam irradiation leads to reduced acute side effects in an in-vivo mouse ear model E. Zahnbrecher 1 , M. Sammer 2 , J. Reindl 2 , C. Greubel 2 , B. Schwarz 2 , C. Siebenwirth 1,2 , D.W.M. Walsh 1,2 , K. Ilicic 1 , J.J. Wilkens 1,3 , S.E. Combs 1,3 , G. Dollinger 2 , T.E. Schmid 1,3 1 Klinikum rechts der Isar, Technische Universität München, Munich, Germany 2 Institut für angewandte Physik und Messtechnik, Universität der Bundeswehr München, Neubiberg, Germany 3 Institute of Innovative Radiotherapy, Helmholtz Zentrum München, Neuherberg, Germany Purpose or Objective In Radiation Oncology, the maximum dose which can be delivered to a certain tumor is often limited by the radiation induced damage in normal tissue surrounding the actual tumor. Proton minibeam radiotherapy aims to minimize normal tissue damage, especially in the entrance channel. Due to beam widening with increasing track length, it leads to a homogeneous dose distribution in the tumor area, which permits tumor control as in conventional proton therapy. Acute side effects of proton minibeam irradiation were examined in an in-vivo mouse ear model to account for immune system, vasculature and higher complexity. In this study, the effect of partially widened proton minibeams was investigated as occurring repair. Results

Conclusion Using RBE 1.1

makes proton therapy dose and dose- dependent predictions less accurate. Our results using a RBE calculation model show that decreased accuracy may have clinical implications, which agrees with published literature (Jones 2012; Jones, 2014), and may affect secondary cancer risk and normal tissue complication probability calculations as well. PO-0961 DNA damage and repair influence tumor sensitivity to diffusing alpha emitters radiation therapy Y. Keisari 1 , R. Etzyoni 1 , H. Bittan 2 , E. Lazarov 2 , M. Efrati 1 , M. Schmidt 2 , T. Cooks 1 , L. Arazi 2 , I. Kelson 2 1 Tel-Aviv University / Faculty of Medicine, Clinical Microbiology and Immunology, Tel-Aviv, Israel 2 Tel Aviv University, School of Physics and Astronomy- Sackler Faculty of Exact sciences, Tel Aviv, Israel Purpose or Objective We developed an alpha radiation based brachytherapy, which provides efficient ablation of solid tumors by alpha radiation. This treatment termed, Diffusing Alpha emitters Radiation Therapy (DaRT) utilizes radium-224 loaded wires, which when inserted into the tumor release by recoil short-lived alpha-emitting atoms. These atoms disperse in the tumor, and spray it with highly destructive alpha radiation. DaRT achieved substantial tumor growth retardation, extended survival, and reduced lung metastases in mice bearing various mouse and human derived tumors. Better tumor control was achieved when DaRT was applied with chemotherapy. Furthermore, tumor ablation by DaRT boosted anti-tumor immune responses.